Autoimmune neutropenia in systemic lupus erythematosus

Abstract

The mechanism of granulocyte depletion in a patient with systemic lupus erythematosus and neutropenia was investigated. Neutrophil kinetic studies showed a shortened intravascular survival (t1/2 of 1.6 hours) in the face of an increased marrow neutrophil pool. IgG bound to the patient's neutrophils, measured by the Fab anti‐F(ab)2 assay, was nearly three times normal. The IgG neutrophil‐binding activity of the patient's serum was elevated in serial samples obtained over two years. In addition, his serum was able to opsonize normal neutrophils for ingestion by other neutrophils as detected by 14C‐1‐glucose oxidation. Enhanced IgG PMN‐binding activity was observed with sucrose density gradient fractions of the patient's serum containing either large complexes (19S or greater in size), intermediate complexes (between 7S and 19S), or monomeric IgG. Only the monomeric IgG fraction from the patient's serum, however, opsonized normal neutrophils for ingestion by other neutrophils. These results support the hypothesis that anti‐cell antibodies were responsible for the neutropenia in this patient by opsonizing neutrophils for ingestion by other phagocytic cells.

Neutrophil-binding immunoglobulin G in systemic lupus erythematosus.

“…The amount of IgG that bound to normal PMN after in vitro incubation with heat-inactivated sera from 36 normal individuals, 6 patients with IgG monoclonal paraproteins, and 38 SLE patients was determined. The IgG-PBA (mean±1 SD) of the normal serum samples was 29.2±8.3 ng IgG/ 106 PMN, as recently published (9). The mean value for the 6 monoclonal IgG sera, whose IgG concentrations varied from 1.4 to 5.8 gm/100 ml, was 30.7±8.5 ng IgG/106 PMN, not significantly increased above normal serum IgG-PBA.…”

“…gradients followed by sedimentation of erythrocytes with 3% dextran, molecular weight 500,000 (Sigma Chemical Co., St. Louis, Mo. ), as described (8,9). Residual erythrocytes were lysed by brief hypotonic shock with 0.2% NaCl.…”

“…This assay, described in detail (9,11), is a quantitative antiglobulin consumption technique that uses the marked solubility difference in 50% saturated ammonium sulfate (SAS) of unbound human 125I-Fab compared to 125I-Fab bound to rabbit antihuman F(ab')2. Human IgG was purified from commercial Cohn fraction II (Schwartz/ Mann Div., Beckton, Dickinson & Co., Orangeburg, N.…”

“…1 ml of normal or SLE serum samples were also fractionated by linear sucrose density gradient (SDG) ultracentrifugation, as described (9). The gradients were harvested and five approximately equal pools were made containing material >19S, 19S, 7S-19S, 7S, and <7S in size.…”

“…The Raji cell assay was kindly carried out by Dr. Argyrios Theofilopoulos (Scripps Clinic and Research Foundation, La Jolla, Calif.) (20). The opsonization assay for anti-PMN antibodies was performed in our laboratory as recently described (9).…”